TY - JOUR
T1 - Pembrolizumab in microsatellite instability-high/mismatch repair deficient (MSI-H/dMMR) and non–MSI-H/non–dMMR advanced endometrial cancer
T2 - Phase 2 KEYNOTE-158 study results
AU - O'Malley, David M.
AU - Bariani, Giovani M.
AU - Cassier, Philippe A.
AU - Marabelle, Aurelien
AU - Hansen, Aaron R.
AU - Acosta, Ana De Jesus
AU - Miller, Wilson H.
AU - Safra, Tamar
AU - Italiano, Antoine
AU - Mileshkin, Linda
AU - Yao, Lili
AU - Gozman, Alexander
AU - Jin, Fan
AU - Maio, Michele
N1 - Publisher Copyright:
© 2024
PY - 2025/2/1
Y1 - 2025/2/1
N2 - Objective: We report updated results with longer follow-up in patients with MSI-H/dMMR endometrial cancer (EC) in cohort D (advanced EC of any MSI/dMMR status) and cohort K (any MSI-H/dMMR advanced solid tumor, except colorectal) of the phase 2 KEYNOTE-158 study (NCT02628067) and the first results from patients with non–MSI-H/non–dMMR advanced EC (cohort D). Methods: Patients received pembrolizumab 200 mg Q3W for ≥35 cycles. The primary endpoint was objective response rate (ORR) per RECIST v1.1 by central review. Secondary endpoints included duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety. Results: As of January 12, 2022, median (range) follow-up in the MSI-H/dMMR (n = 94) and non–MSI-H/non–dMMR (n = 96) groups was 54.5 (14.7–71.4) and 68.3 (64.3–71.9) months, respectively. The ORR (95 % CI) was 50 % (40 %–61 %) in the MSI-H/dMMR group; 15 patients (16 %) experienced a complete response, 32 (34 %) experienced a partial response. The ORR (95 % CI) in the non–MSI-H/non–dMMR group was 7 % (3 %–14 %); 7 patients (7 %) experienced a partial response, none experienced a complete response. The estimated 4-year DOR rates were 66 % and 56 %, respectively. Median PFS was 13.1 (95 % CI, 4.3–25.7) months in the MSI-H/dMMR group and 2.1 (95 % CI, 2.1–2.2) months in the non–MSI-H/non–dMMR group. Median OS was 65.4 (95 % CI, 29.5–not reached) and 11.1 (95 % CI, 8.1–15.3) months, respectively. Toxicity was manageable in both groups. Conclusions: These results continue to support pembrolizumab as a standard-of-care option for MSI-H/dMMR advanced EC in patients with disease progression following prior systemic therapy who are not candidates for curative surgery or radiation.
AB - Objective: We report updated results with longer follow-up in patients with MSI-H/dMMR endometrial cancer (EC) in cohort D (advanced EC of any MSI/dMMR status) and cohort K (any MSI-H/dMMR advanced solid tumor, except colorectal) of the phase 2 KEYNOTE-158 study (NCT02628067) and the first results from patients with non–MSI-H/non–dMMR advanced EC (cohort D). Methods: Patients received pembrolizumab 200 mg Q3W for ≥35 cycles. The primary endpoint was objective response rate (ORR) per RECIST v1.1 by central review. Secondary endpoints included duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety. Results: As of January 12, 2022, median (range) follow-up in the MSI-H/dMMR (n = 94) and non–MSI-H/non–dMMR (n = 96) groups was 54.5 (14.7–71.4) and 68.3 (64.3–71.9) months, respectively. The ORR (95 % CI) was 50 % (40 %–61 %) in the MSI-H/dMMR group; 15 patients (16 %) experienced a complete response, 32 (34 %) experienced a partial response. The ORR (95 % CI) in the non–MSI-H/non–dMMR group was 7 % (3 %–14 %); 7 patients (7 %) experienced a partial response, none experienced a complete response. The estimated 4-year DOR rates were 66 % and 56 %, respectively. Median PFS was 13.1 (95 % CI, 4.3–25.7) months in the MSI-H/dMMR group and 2.1 (95 % CI, 2.1–2.2) months in the non–MSI-H/non–dMMR group. Median OS was 65.4 (95 % CI, 29.5–not reached) and 11.1 (95 % CI, 8.1–15.3) months, respectively. Toxicity was manageable in both groups. Conclusions: These results continue to support pembrolizumab as a standard-of-care option for MSI-H/dMMR advanced EC in patients with disease progression following prior systemic therapy who are not candidates for curative surgery or radiation.
KW - Advanced endometrial cancer
KW - DNA mismatch repair deficiency
KW - Microsatellite instability-high
KW - Pembrolizumab
UR - http://www.scopus.com/inward/record.url?scp=85215400685&partnerID=8YFLogxK
U2 - 10.1016/j.ygyno.2024.12.020
DO - 10.1016/j.ygyno.2024.12.020
M3 - Article
AN - SCOPUS:85215400685
SN - 0090-8258
VL - 193
SP - 130
EP - 135
JO - Gynecologic Oncology
JF - Gynecologic Oncology
ER -